NCT03923725

Brief Summary

A partially blinded randomised controlled non-inferiority trial comparing the efficacy, tolerability and safety of Triple ACTs artemether-lumefantrine+amodiaquine (AL+AQ) and artesunate-mefloquine+piperaquine (ASMQ+PPQ) and the ACTs artemether-lumefantrine+placebo (AL+PBO), artesunate-mefloquine+placebo (ASMQ+PBO) (with single-low dose primaquine in some sites) for the treatment of uncomplicated Plasmodium falciparum malaria to assess and compare their efficacy, safety, tolerability.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2,583

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Sep 2020

Typical duration for phase_3

Geographic Reach
8 countries

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 9, 2019

Completed
14 days until next milestone

First Posted

Study publicly available on registry

April 23, 2019

Completed
1.4 years until next milestone

Study Start

First participant enrolled

September 1, 2020

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 15, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 15, 2024

Completed
Last Updated

November 18, 2025

Status Verified

November 1, 2025

Enrollment Period

3.5 years

First QC Date

April 9, 2019

Last Update Submit

November 14, 2025

Conditions

Keywords

ArtemetherLumefantrineAmodiaquineArtesunatePiperaquineMefloquineTriple Artemisinin-based Combination Therapy (TACT)

Outcome Measures

Primary Outcomes (1)

  • 42 days Efficacy defined as PCR corrected adequate clinical and parasitological response (ACPR).

    42 days Efficacy defined as PCR corrected adequate clinical and parasitological response (ACPR).

    42 days

Secondary Outcomes (17)

  • 63-day PCR corrected and uncorrected efficacy

    63 days

  • 42-day PCR uncorrected efficacy

    42 days

  • Parasite clearance half-life

    3 Days

  • Proportion of subjects with microscopically detectable P. falciparum parasitaemia

    Day 3

  • Fever clearance time

    63 Days

  • +12 more secondary outcomes

Other Outcomes (13)

  • Comparison of 63-day vs 42-day PCR corrected and uncorrected efficacy

    63 days

  • Proportions of recurrent infections

    63 days

  • Proportions of specimens collected at baseline with parasites carrying mutations

    baseline

  • +10 more other outcomes

Study Arms (4)

Artemether-lumefantrine+amodiaquine (AL+AQ)

EXPERIMENTAL

Triple ACTs

Drug: Artemether-lumefantrine+ Amodiaquine (AL+AQ)

artemether-lumefantrine+placebo (AL+PBO)

ACTIVE COMPARATOR

ACTs

Drug: Artemether-lumefantrine + placebo (AL+PBO)

Artesunate-mefloquine+Piperaquine (AS-MQ+PPQ)

EXPERIMENTAL

Triple ACTs

Drug: Artesunate-mefloquine+piperaquine (AS-MQ+PPQ)

Artesunate-mefloquine+placebo (AS-MQ+PBO)

ACTIVE COMPARATOR

ACTs

Drug: Artesunate-mefloquine+placebo (AS-MQ+PBO)

Interventions

AL: Currently available as dispersible tablets containing 20 mg of artemether and 120 mg of lumefantrine, in a fixed-dose combination formulation. The flavoured dispersible tablet paediatric formulation facilitates use in young children. The dose of artemether-lumefantrine is administered approaching the WHO-recommended target ranges of artemether 5-24 mg/kg and lumefantrine 29-144 mg/kg over 3 days. AQ: is available as dispersible tablets of 40 mg. The weight-based treatment schedule aims for a dosage of approximately 10mg (4.5-15mg)/kg/day amodiaquine for three days.

Artemether-lumefantrine+amodiaquine (AL+AQ)

AL: Currently available as dispersible tablets containing 20 mg of artemether and 120 mg of lumefantrine, in a fixed-dose combination formulation. The flavoured dispersible tablet paediatric formulation facilitates use in young children. The dose of artemether-lumefantrine is administered approaching the WHO-recommended target ranges of artemether 5-24 mg/kg and lumefantrine 29-144 mg/kg over 3 days. PBO: Placebo tablets for amodiaquine are identical in size, shape and color to the amodiaquine tablets.

artemether-lumefantrine+placebo (AL+PBO)

AS: Artesunate will be administered according to an optimised dosing schedule using tablets of 32 or 100 mg artesunate with a dosing target of 4 mg/kg/day. MQ: Mefloquine will be administered according to an optimised dosing schedule using tablets of 70 or 220 mg mefloquine hydrochloride with a dosing target of 8.3 mg/kg/day. PPQ: Piperaquine will be administered according to an optimised dosing schedule using tablets of 160 or 500 mg of piperaquine tetraphosphate. The weight-based treatment aims for a dosage of approximately. * 24 mg/kg/day in patients \<25 kg (range 16.0 - 32.0 mg/kg) piperaquine for three days, thereby approaching the WHO-recommended target range of 20 - 32 mg/kg per day. * 18 mg/kg/day in patients ≥25 kg (range 15.0 - 29.4 mg/kg) piperaquine for three days, thereby approaching the WHO-recommended target range of 16 - 27 mg/kg per day.

Artesunate-mefloquine+Piperaquine (AS-MQ+PPQ)

AS: Artesunate will be administered according to an optimised dosing schedule using tablets of 32 or 100 mg artesunate with a dosing target of 4 mg/kg/day. MQ: Mefloquine will be administered according to an optimised dosing schedule using tablets of 70 or 220 mg mefloquine hydrochloride with a dosing target of 8.3 mg/kg/day. PBO: Placebo tablets for piperaquine are identical in size, shape and colour to the piperaquine tablets.

Artesunate-mefloquine+placebo (AS-MQ+PBO)

Eligibility Criteria

Age6 Months - 12 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Male or female, aged ≥6 months to \<12 years (For Gambia, Rwanda sites only: ≥6 months)
  • Ability to take oral medication
  • Acute uncomplicated P. falciparum monoinfection
  • Asexual P. falciparum parasitaemia: 1,000/µL to ≤10% parasitaemia, determined on a peripheral blood film (At Gambia, Rwanda sites only: For subjects ≥12 years - 1000/µL to 200,000/µL)
  • Fever defined as ≥ 37.5°C tympanic temperature or a history of fever within the last 24 hours
  • Written informed consent by the subject or by parent/guardian in case of children lower than the age of consent and assent if required (per local regulations)
  • Willingness and ability of the subjects or parents/guardians to comply with the study protocol for the duration of the study

You may not qualify if:

  • Signs of severe malaria (adapted from WHO criteria)
  • Patients not fulfilling criteria for severe malaria but with another indication for parenteral antimalarial treatment at the discretion of the treating physician
  • Haematocrit \<15% at screening (For Gambia, Rwanda sites only: For subjects ≥12 years - Haematocrit \<20% at screening)
  • Subjects who have received artemisinin or a derivative within the previous 7 days OR lumefantrine or amodiaquine within the previous 14 days OR mefloquine or piperaquine within the previous 30 days
  • In applicable countries: use of seasonal malaria chemoprophylaxis (SMC) within the last 14 days.
  • Acute illness other than malaria requiring systemic treatment
  • Severe acute malnutrition (in Niger only - only those patients with Severe Acute Malnutrition and complications requiring inpatient nutritional treatment will be excluded)
  • Known HIV infection
  • Known tuberculosis infection
  • For females: post-menarche (For Gambia, Rwanda sites only: females who are pregnant, trying to get pregnant or are lactating)
  • History of allergy or known contraindication to any of the study drugs, including neuropsychiatric disorders and epilepsy
  • Previous splenectomy
  • Enrolment in DeTACT in the previous 3 months
  • Participation in another interventional study in the previous 3 months

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Institut des Sciences et Techniques (INSTech)

Bobo-Dioulasso, Burkina Faso

Location

Kinshasa School of Public Health

Kinshasa, BP 11850 Kin, Democratic Republic of the Congo

Location

Centre National de Formation et de Recherche en Santé Rurale de Mafèrinyah

Conakry, B.P. 2649, Guinea

Location

Centre for Malaria and Other Tropical Diseases (CEMTROD)

Ilorin, Kwara State, 1459, Nigeria

Location

Epicentre Niger

Niamey, BP: 13 330, Niger

Location

College of Medicine and Health Sciences, University of Rwanda

Kigali, Rwanda

Location

National Institute For Medical Research (NIMR), Tanga Medical Research Centre

Tanga, Tanzania

Location

MRC Unit The Gambia at LSHTM

Fajara, City of Banjul, 273, The Gambia

Location

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

MalariaProtozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

ArtemetherArtemisininsReactive Oxygen SpeciesFree RadicalsInorganic ChemicalsOrganic ChemicalsLumefantrineFluorenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSesquiterpenesTerpenesPolycyclic CompoundsDrug CombinationsPharmaceutical Preparations

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 9, 2019

First Posted

April 23, 2019

Study Start

September 1, 2020

Primary Completion

March 15, 2024

Study Completion

March 15, 2024

Last Updated

November 18, 2025

Record last verified: 2025-11

Data Sharing

IPD Sharing
Will share

With participant's consent, participant's data and results from blood analyses stored in the database may be shared according to the terms defined in the MORU data sharing policy with data repositories such as the WorldWide Antimalarial Resistance Network (WWARN, terms of submission here: http://www.wwarn.org/tools-resources/terms-submission) or other researchers to use in the future. All personal information will be anonymised so that no individual can be identified from their treatment records, through interviews, or from mapping data.

Time Frame
After completion of trial activities and reporting.
Access Criteria
MORU Data Sharing Policy https://www.tropmedres.ac/units/moru-bangkok/bioethics-engagement/data-sharing WWARN Terms of Data Access https://www.wwarn.org/tools-resources/terms-data-access

Locations